Discordance in Oncotype DX Breast Recurrence Score® Results for Bilateral Breast Cancer.

BACKGROUND: The Oncotype DX Breast Recurrence Score® assay is a clinically useful tool to determine the benefit of chemotherapy in the treatment of early-stage, hormone-receptor-positive breast cancer. Bilateral breast cancer (BBC) is found in ~ 5% of patients with breast cancer, and data regarding discordance of Oncotype DX results between BBC defined by current TAILORx subgroups are limited. Our goals are to study the rate of Oncotype DX discordance between BBC and investigate whether such differences can affect chemotherapy treatment discussions. METHODS: Patients with BBC were identified in US samples submitted to Genomic Health for 21-gene testing between January 2019 and July 2020. The risk categories were defined as 0-25 and 26-100 as well as 0-17, 18-30, and 31-100 for all patients. Subgroup analysis was also performed for node-negative women age ≤ 50 years with Recurrence Score results of 0-15, 16-20, 21-25, and 26-100. RESULTS: 944 BBC patients with known nodal status (702 node negative, 242 node positive) were identified and included. Among node-negative patients aged > 50 years, the rate of discordance in Recurrence Score by group (0-25 and 26-100) was 4.2% (n = 598). For node-negative patients aged ≤ 50 years, the risk group was discordant in < 3% when considering the risk grouping of 0-25 and 26-100. However, upon subgroup analysis based on TAILORx analysis, the rate of discordance was 48.1% in these younger patients (n = 104). CONCLUSIONS: This study shows that a clinically relevant rate of discordance in Oncotype DX results in patients with BBC may impact medical decision-making regarding chemotherapy.

Molecular characterization of breast cancer needle core biopsy specimens by the 21-gene Breast Recurrence Score test.

BACKGROUND AND OBJECTIVE: Recent COVID-19 pandemic guidelines recommend genomic assessment of core biopsies to help guide treatment decisions in estrogen receptor (ER)-positive early-stage breast cancer. Herein we characterize biopsy and excisional breast cancer specimens submitted for 21-gene testing. METHODS: US samples submitted to Genomic Health for 21-gene testing (01/2004-04/2020) were assessed by pathologists and analyzed by a standardized quantitative reverse transcription-polymerase chain reaction. Predefined cutoffs were: ESR1 (positive ≥6.5), PGR (positive ≥5.5), and ERBB2 (negative <10.7). ER status by immunohistochemistry (IHC) and lymph node status were determined locally. Median and interquartile range were reported for continuous variables, and total and percent for categorical variables. Distributions were assessed overall, by age, and by nodal involvement. RESULTS: Of 919 701 samples analyzed, 13% were biopsies and 87% were excisions. Initial assay success rates were 94.5% (biopsies) and 97.3% (excisions). ER IHC concordance with central ESR1 was 96.8% (biopsies) and 97.6% (excisions). Biopsy and excisional medians were: Recurrence Score results 16 (each); ESR1 10.2 (each); PGR 7.7 and 7.6; ERBB2 9.4 and 9.2, respectively. CONCLUSIONS: Biopsy submissions for 21-gene testing are common and consistently generate results that are very similar to the experience with excisions. The 21-gene test can be performed reliably on core biopsies.

Correlation between percutaneous biopsy and final histopathology for retroperitoneal sarcoma: a single-centre study.

BACKGROUND: Retroperitoneal sarcomas are rare soft tissue tumours accounting for 10-15% of soft tissue sarcomas. Patient prognosis and treatment recommendations (including extent of surgery and neoadjuvant strategies) are determined by the pre-operative histopathological subtype and grade obtained from biopsy and thus it is important to understand the accuracy of biopsy in retroperitoneal masses. METHODS: This study presents a case series of primary retroperitoneal sarcomas managed at Peter MacCallum Cancer Centre (PMCC) between 2008 and 2019. Statistical analyses were performed to determine correlation between histopathology from percutaneous biopsy and surgical excision. RESULTS: A total of 117 patients who underwent percutaneous core biopsy and surgical excision of retroperitoneal sarcoma were included. Diagnostic accuracy varied with histopathological diagnosis, but overall precise concordance between biopsy and final histopathology was seen in 61% (κ = 0.57). Biopsy was most sensitive for identifying well-differentiated liposarcoma (WDLPS) (sensitivity 85%, 95% CI 0.06-0.96) and leiomyosarcoma (sensitivity 81%, 95% CI 0.54-0.96) and was least sensitive for identifying de-differentiated liposarcoma (DDLPS) (sensitivity 40%, 95% CI 0.25-0.56). Overall agreement between biopsy and final histopathology increased with use of PET/CT scan pre-biopsy and with use of fluorescence in situ hybridisation testing on biopsy, however, neither test improved recognition of de-differentiated components within WD/DDLPS on core biopsy. CONCLUSIONS: Pre-operative biopsy is important for clinical decision making in the treatment of retroperitoneal sarcoma. A significant portion of patients with a WDLPS will have a de-differentiated component identified at the time of resection that was not identified on initial biopsy.

Carotid artery displacement and cardiovascular disease risk in the Multi-Ethnic Study of Atherosclerosis.

Novel technology permits quantification of common carotid artery (CCA) displacement, which is traditionally ignored. We evaluated associations with CCA displacement and cardiovascular disease (CVD) risk and events in a large, multi-ethnic cohort. Right CCA longitudinal displacement (LD), transverse displacement (TD), and grayscale median (GSM) were evaluated using ultrasound speckle-tracking and texture analysis software in 2050 participants. Regression analyses were used to define relationships between CCA LD, TD, GSM, and CVD risk factors. Cox proportional hazards models were used to assess relationships between LD, TD, and incident CVD events. Participants were mean (SD) 64 (10) years old. There were 791 cases with a CVD event over a 12-year median follow-up. The mean LD was 0.29 (0.20) mm. In multivariable models including age, sex, race/ethnicity, heart rate, and CVD risk factors, LD was associated positively with active smoking (ß = 0.08, p < 0.001) and inversely with black (ß = -0.08, p < 0.001), Chinese (ß = -0.05, p < 0.001), and Hispanic (ß = -0.04, p < 0.05) race/ethnicities relative to white individuals, heart rate (ß = -0.03/10 beats/min, p < 0.001), and diastolic blood pressure (ß = -0.01/5 mmHg, p < 0.05). In fully adjusted models, LD and TD were associated with GSM (p < 0.01), but neither predicted incident CVD events (LD: hazard ratio (HR) 0.77 [0.48 to 1.24], p = 0.3; TD: HR 1.12 [0.8 to 1.57], p = 0.5). CCA LD and TD are associated with race/ethnicity and CVD risk factors but not incident CVD events. LD and TD are not measures of arterial stiffness but their association with GSM suggests that lower LD and TD may be related to structural changes within the carotid arterial wall.

A Retrospective Comparison of Transrectal and Transperineal Prostate Biopsies: Experience of a Single Surgeon.

Background: Transrectal ultrasound-guided prostate biopsy (TRUS) is the gold standard for undertaking prostate biopsy, however, it has been associated with higher rates of post-biopsy sepsis than transperineal prostate biopsy (TP). Objective: To compare complication rates between transrectal prostate biopsy and TP for a single surgeon. Materials and Methods: Data were collected for all prostate biopsies undertaken by a single experienced urologist through his private rooms between February 2012 and March 2018. In total, 693 cases were included (560 individual men) in the final analysis (transrectal = 276 and transperineal = 417). All patients were followed up 2 weeks post-biopsy, and complications were recorded (sepsis, urinary tract infection [UTI], bleeding, and acute urinary retention [AUR]). Results: Complications occurred in 37 cases (transrectal = 3 and transperineal = 34). Sepsis occurred in one case following transrectal biopsy (0.36%) and two cases following TP (0.48%). UTI occurred in two cases following transrectal biopsy (0.72%) and two cases following transperineal (0.48%). Bleeding occurred in one case following TP (0.24%). The most common complication was AUR, which occurred in 28 cases following TP (6.71%). Conclusions: Data from this study compared complication rates for both transperineal and transrectal prostate biopsies in a single-surgeon study.

Spot Urine Sodium-to-Potassium Ratio Is a Predictor of Stroke.

Background and Purpose- Dietary sodium reduction with concurrent increase in potassium intake is a current public health priority to reduce risk of cardiovascular events. This study explored associations between the spot urine sodium-to-potassium ratio and cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) longitudinal cohort. Methods- The MESA is a prospective cohort study of 6814 adults from 4 ethnic groups (European-, Asian-, African- and Hispanic-American) with a mean age of 62 (±10.2) years and an average of 11.7 (±2.2) years of follow-up. Participants were free of clinical cardiovascular disease at baseline. Spot urine sodium and potassium excretion, as a marker of dietary intake, was collected at baseline. The impact of urinary sodium-to-potassium ratio on adjudicated cardiovascular events was assessed using Cox proportional hazards models. Results- Only 39% of MESA participants had a urinary sodium-to-potassium ratio ≤1, and these participants experienced only 74 of the 236 strokes. A sodium-to-potassium ratio >1 was associated with a hazard ratio of 1.47 (95% CI,1.07-2.00) for risk of stroke, adjusting for age, sex, race, cardiovascular risk factors, socio-demographic characteristics, body size, and kidney function. Conclusions- The spot urine sodium-to-potassium ratio (measurable in routine care) is associated with stroke. A urine sodium-to-potassium ratio of ≤1, may be related to a clinically relevant reduction in stroke risk and is a feasible target for health interventions.

Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).

Aims: While coronary artery calcium (CAC) has been extensively validated for predicting clinical events, most outcome studies of CAC have evaluated coronary heart disease (CHD) rather than atherosclerotic cardiovascular disease (ASCVD) events (including stroke). Also, virtually all CAC studies are of short- or intermediate-term follow-up, so studies across multi-ethnic cohorts with long-term follow-up are warranted prior to widespread clinical use. We sought to evaluate the contribution of CAC using the population-based MESA cohort with over 10 years of follow-up for ASCVD events, and whether the association of CAC with events varied by sex, race/ethnicity, or age category. Methods and results: We utilized MESA, a prospective multi-ethnic cohort study of 6814 participants (51% women), aged 45-84 years, free of clinical CVD at baseline. We evaluated the relationship between CAC and incident ASCVD using Cox regression models adjusted for age, race/ethnicity, sex, education, income, cigarette smoking status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes, lipid-lowering medication, systolic blood pressure, antihypertensive medication, intentional physical exercise, and body mass index. Only the first event for each individual was used in the analysis. Overall, 500 incident ASCVD (7.4%) events were observed in the total study population over a median of 11.1 years. Hard ASCVD included 217 myocardial infarction, 188 strokes (not transient ischaemic attack), 13 resuscitated cardiac arrest, and 82 CHD deaths. Event rates in those with CAC = 0 Agatston units ranged from 1.3% to 5.6%, while for those with CAC > 300, the 10-year event rates ranged from 13.1% to 25.6% across different age, gender, and racial subgroups. At 10 years of follow-up, all participants with CAC > 100 were estimated to have >7.5% risk regardless of demographic subset. Ten-year ASCVD event rates increased steadily across CAC categories regardless of age, sex, or race/ethnicity. For each doubling of CAC, we estimated a 14% relative increment in ASCVD risk, holding all other risk factors constant. This association was not significantly modified by age, sex, race/ethnicity, or baseline lipid-lowering use. Conclusions: Coronary artery calcium is associated strongly and in a graded fashion with 10-year risk of incident ASCVD as it is for CHD, independent of standard risk factors, and similarly by age, gender, and ethnicity. While 10-year event rates in those with CAC = 0 were almost exclusively below 5%, those with CAC ≥ 100 were consistently above 7.5%, making these potentially valuable cutpoints for the consideration of preventive therapies. Coronary artery calcium strongly predicts risk with the same magnitude of effect in all races, age groups, and both sexes, which makes it among the most useful markers for predicting ASCVD risk.

Local therapy for triple-negative breast cancer: a comprehensive review.

Owing to its aggressive course, triple-negative breast cancer remains an important clinical issue of current interest compared with hormone-receptor positive subtypes. Recent research has focused on determining the optimal local therapy (breast conversation therapy vs mastectomy) for this cancer subtype. In this overview, we examine outcomes based on immunohistochemistry, gene expression profiles, type of local therapy and in the era of neoadjuvant chemotherapy. Based on multiple observational reports risk for locoregional recurrence appears to be similar to reported outcomes in other subtypes. However, distant recurrence continues to be a significant concern for triple-negative breast cancer, indicating the need for better systemic therapies. To date, insufficient evidence exists to determine whether breast conserving therapy or mastectomy results in superior outcomes.

Circulating Des-gamma-carboxy prothrombin is not associated with cardiovascular calcification or stiffness: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Vitamin K-dependent protein (VKDP) activity may have a role in preventing cardiovascular calcification, but has not previously been studied in large, generally healthy populations. METHODS: Using an elevated ankle-brachial index (ABI) as a measure of medial vascular calcification, we performed a case-cohort analysis within the Multi-Ethnic Study of Atherosclerosis, measuring Des-gamma-carboxy prothrombin (DCP) to estimate VKDP activity. In secondary analyses of the weighted subcohort, we examined the cross-sectional associations between DCP and prevalent vascular calcification of the coronary vessels, aortic and mitral valves, and aortic wall, and with vascular stiffness. RESULTS: In adjusted analysis, cases (n = 104) had 0.21 ng/ml (-0.94-0.52) lower DCP concentrations than the subcohort (n = 613). Furthermore, amongst the 717 participants in the weighted cohort, VKDP activity was not associated with coronary artery, mitral valve, aortic valve or aortic wall calcification, nor was it associated with vascular stiffness. CONCLUSIONS: Our negative results do not support a role of circulating VKDP activity in cardiovascular calcification in community-dwelling adults.

Management algorithm for HIV-associated parotid lymphoepithelial cysts.

We report an evidence-based management algorithm for benign lymphoepithelial cysts (BLEC) of the parotid glands in HIV patients based on long-term outcomes after radiation therapy. From 1987 to 2013, 72 HIV-positive patients with BLEC of the parotid glands treated at our institutions were identified and their medical records were reviewed and analyzed. The primary endpoint of our study was to determine a dose response in HIV patients with BLEC. In group A (≤18 Gy), which received a median dose of 10 Gy (8-18), overall response (OvR), complete response (CR), partial response (PR), and local failure (LF) was experienced by 7, 7, 0, and 93 %, respectively. In group B (≥22.5 Gy), which received a median dose of 24 Gy (22.5-30), OvR, CR, PR, and LF was experienced by 88, 65, 23, and 12 %. Logistic regression revealed that higher dose (≥22.5 Gy) predicted for cosmetic control (p = 0.0003). Multiple regression analysis revealed higher dose predicted for cosmetic control (p = 0.0001) after adjusting for confounding variables (age, gender, race, HAART use, BLEC duration, and fractionation size). No patients in either group experienced RTOG grade ≥3 toxicities. A radiation dose of 24 Gy delivered in 12-16 fractions of 1.5-2 Gy per fraction provides long-term cosmetic control in HIV-positive patients with BLEC of the parotid glands.

HIV and coronary artery calcium score: comparison of the Hawaii Aging with HIV Cardiovascular Study and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts.

OBJECTIVES: To determine the association of HIV, immunologic, and inflammatory factors on coronary artery calcium (CAC), a marker of subclinical atherosclerosis. METHODS: Cross-sectional study comparing baseline data of males from Hawaii Aging with HIV - Cardiovascular Study (HAHCS) with the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The cohorts were pooled to determine effects of HIV on CAC and explore immunologic and inflammatory factors that may explain development of CAC in HIV. Multivariable regression models compared CAC prevalence in HAHCS with MESA adjusting for coronary heart disease (CHD) risk profiles. RESULTS: We studied 100 men from HAHCS and 2733 men from MESA. Positive CAC was seen in 58% HAHCS participants and 57% MESA participants. Mean CAC was 260.8 in HAHCS and 306.5 in MESA. Using relative risk (RR) regression, HAHCS participants had a greater risk (RR = 1.20, P < 0.05) of having positive CAC than MESA when adjusting for age, smoking status, diabetes, antihypertensive therapy, BMI, systolic blood pressure, total cholesterol, and HDL cholesterol. Among participants with positive CAC, HIV infection was not associated with larger amounts of CAC. Among HAHCS participants, current HIV viral load, CD4, length of HIV, interleukin 6 (IL-6), fibrinogen, C-reactive protein (CRP), and D-dimer were not associated with the presence or amount of CAC. DISCUSSION: HIV was independently associated with a positive CAC in men with increased likelihood occurring between 45 and 50 years of age. Current HIV viral load, CD4 count, length of HIV, and inflammatory markers were unrelated to either presence or amount of CAC.

An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort.

BACKGROUND: Accurate risk assessment of atherosclerotic cardiovascular disease (ASCVD) is essential to effectively balance the risks and benefits of therapy for primary prevention. OBJECTIVE: To compare the calibration and discrimination of the new American Heart Association (AHA) and American College of Cardiology (ACC) ASCVD risk score with alternative risk scores and to explore preventive therapy as a cause of the reported risk overestimation using the AHA-ACC-ASCVD score. DESIGN: Prospective epidemiologic study of ASCVD. SETTING: MESA (Multi-Ethnic Study of Atherosclerosis), a community-based, sex-balanced, multiethnic cohort. PATIENTS: 4227 MESA participants aged 50 to 74 years and without diabetes at baseline. MEASUREMENTS: Observed and expected events for the AHA-ACC-ASCVD score were compared with 4 commonly used risk scores-and their respective end points-in MESA after a 10.2-year follow-up. RESULTS: The new AHA-ACC-ASCVD and 3 older Framingham-based risk scores overestimated cardiovascular events by 37% to 154% in men and 8% to 67% in women. Overestimation was noted throughout the continuum of risk. In contrast, the Reynolds Risk Score overestimated risk by 9% in men but underestimated risk by 21% in women. Aspirin, lipid-lowering or antihypertensive therapy, and interim revascularization did not explain the overestimation. LIMITATION: Comparability of MESA with target populations for primary prevention and possibility of missed events in MESA. CONCLUSION: Of the 5 risk scores, 4, including the new AHA-ACC-ASCVD score, showed overestimation of risk (25% to 115%) in a modern, multiethnic cohort without baseline clinical ASCVD. If validated, overestimation of ASCVD risk may have substantial implications for individual patients and the health care system. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Is uniport thoracoscopic surgery less painful than multiple port approaches?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients undergoing Video-Assisted Thoracoscopic Surgery (VATS), does a uniport (single-port) or multiport technique convey benefit in terms of postoperative pain?' Altogether, 255 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studies, study type, relevant outcomes and results of these tables are tabulated. All the available evidence is from small, non-randomized studies. Many were retrospective and methodologically weak. Most studied minor thoracic surgical procedures and a few compare the two approaches in major pulmonary resections. One of the studies compared pain at 24 h for uniport [mean Visual Analogue Scale (VAS) >4.4] and three-port VATS (mean VAS 6.2), for different procedures including lung biopsy and surgery for pneumothorax (P = 0.035). Another study compared pain in the first 36-h post-sympathectomy and found mean pain scores of 0.8 in the uniport group and 1.2 in the two-port group (P = 0.025). Six studies exclusively compared the VAS between uniport and three-port VATS for primary spontaneous pneumothorax. Two studies found no significant difference in pain scores and four found a statistically significant reduction in early postoperative pain scores. One study found that pain scores were similar for lung volume reduction surgery. Two studies compared the mean VAS and morphine use between uniportal and multiportal lobectomies; however, there were no statistically significant differences. From the papers identified in our search, we conclude that uniport VATS may have a small clinical effect in reducing postoperative pain, with the majority of papers looking at the first 72 h following surgery. Often the VAS score was only improved in the uniport patients by 1-2 points, and the studies did not find statistically significant results throughout their investigations, especially when looking at follow-up pain scores. Around one-third of the chosen papers did not find any statistically significant results. Further studies are needed before single-port can be recommended as less painful than multiport thoracoscopic surgery.

25-year follow-up of HIV-positive patients with benign lymphoepithelial cysts of the parotid glands: a retrospective review.

AIM: To report long-term outcomes for HIV-positive patients who underwent radiation therapy (RT) for benign lymphoepithelial cysts (BLEC) of the parotid glands. PATIENTS AND METHODS: In this single institution retrospective study of HIV-associated BLEC of the parotids, the medical records of 37 HIV-positive patients who were treated with RT between 1987-2012 were reviewed. Patients were stratified into two groups; group A consisted of 15 patients (40.5%) who received a total dose of ≤18Gy, with a median dose 10 Gy (range 8-18Gy), and group B consisted of 22 patients (59.5%) who received a total dose of 24 Gy. In addition to dosing information, additional patient data were collected, including demographics, HAART compliance, follow-up, and re-treatment status. RESULTS: The median age at the time of treatment was 41 (range=7-70) years. With a median follow-up of 35 (range=12-75) months for the entire cohort, the complete response (CR) and partial response (PR) rates were 35% and 8%, respectively. All but one of 15 patients in Group A (lower total dose) eventually experienced local failure with the re-emergence of parotid hypertrophy. Among the patients in group B (higher total dose of 24 Gy), 55%, 13%, and 32% experienced CR, PR, and LF, respectively. Median times to failure in groups A and B were 7 and 20 months, respectively (p<0.0001). Similarly, logistic regression test revealed the higher dose to be associated with better response rate (i.e. CR or PR) (p<0.0001), which was also statistically significant (p=0.03) after adjusting for confounding variables (age, race, gender, HAART use, and fractionation). CONCLUSION: A total dose of 24 Gy continues to be recommended for durable cosmetic control of BLEC of the parotid glands that is associated with HIV-seropositivity.

Comprehensive head and neck radiotherapy dose-volume constraints do not apply to smaller volumes.

AIM: To investigate the impact of definitive radiation therapy (RT) in the management of early glottic cancer on clinical RT-induced dysphagia (RID) and carotid vasculopathy (RICV). PATIENTS AND METHODS: This is a single-institution retrospective study. From January 1997 to 2010, 253 patients, with early glottic cancer, underwent RT with (60)Co or LINAC-6 MV photons. RT fields with wedge pair and daily 5-mm bolus were applied in all patients treated with 6-MV photons to avoid under-dose of the anterior laryngeal structures. The whole larynx (LX), pharyngeal constrictors (PCs), and carotid arteries (CA) were contoured and dose-volume histograms (DVHs) were generated to assess the delivered dose. The median age of patients was 65 years (range; 28-93), Caucasians were 80%, males were 87%, and 23% had T2 lesions. RESULTS: After a median follow-up of seven years (range; 1.5-12), the median dose and fraction size delivered to the LX were 63 and 2.25 Gy, respectively. The mean doses to the LX, PC, and CA were 57 Gy delivered to 34 cm(3), 54 Gy to 15 cm(3), and 60 Gy to 4 cm(3), respectively. The LX, PC and CA V60 and V65 were (77 and 71), (70 and 52) and (84 and 51), respectively. Patients with acute dysphagia grades 1, 2, and 3 or more were 81, 19%, and zero, respectively; none had clinically RID or RICV. CONCLUSION: Small-volume RT up to 67.5 Gy at 2.25 Gy per fraction, is not a predictor of RID or RICV. Separate delineation of the aforementioned critical structures, as well as others, may better identify dose tolerances to maintain function and further prioritize the importance of structures in RID and RICV.

Lack of adjuvant radiotherapy may increase risk of retropharyngeal node recurrence in patients with squamous cell carcinoma of the head and neck after transoral robotic surgery.

Purpose. Transoral robotic surgery (TORS) has increased in popularity in the management of squamous cell carcinoma of the head and neck. However, TORS does not address the neck or retropharyngeal nodes (RPN). In the current report, we highlight the impact of the lack of adjuvant radiotherapy on RPN recurrence after TORS. Materials and Methods. A 58-year-old Caucasian male presented with squamous cell carcinoma of the head and neck of unknown primary. He was offered radiotherapy as a definitive management for clinical stage T0N2aM0, stage IVA, but he opted to left neck dissection. Follow-up PET-CT scan revealed recurrence in the left base of tongue and right level II lymph node. He was offered radiotherapy which he declined and opted to TORS and right neck dissection. Follow-up PET-CT scan showed recurrence in left RPN for which he underwent salvage concurrent chemoradiotherapy to 70 Gy. Results. After a followup of 9 months from the date of salvage chemoradiotherapy completion, the patient is with no evidence of disease. Conclusions. TORS followed by adjuvant radiotherapy seems reasonable in the context of squamous cell carcinoma of the head and neck due to the odds of RPN involvement. Further reports are warranted to optimize post-TORS adjuvant treatment.

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

OBJECTIVES: Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). METHODS: Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. RESULTS: We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. CONCLUSIONS: We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs.

Progression of coronary calcium and incident coronary heart disease events: MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES: The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. BACKGROUND: CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. METHODS: We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. RESULTS: A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. CONCLUSIONS: Progression of CAC is associated with an increased risk for future hard and total CHD events.

Comparison of beta-tubulin mRNA and protein levels in 12 human cancer cell lines.

Antimitotic drugs are chemotherapeutic agents that bind tubulin and microtubules. Resistance to these drugs is a major clinical problem. One hypothesis is that the cellular composition of tubulin isotypes may predict the sensitivity of a tumor to antimitotics. Reliable and sensitive methods for measuring tubulin isotype levels in cells and tissues are needed to address this hypothesis. Quantitative measurements of tubulin isotypes have frequently relied upon inferring protein amounts from mRNA levels. To determine whether this approach is justified, protein and mRNA levels of beta-tubulin isotypes from 12 human cancer cell lines were measured. This work focused on only beta-tubulin isotypes because we had readily available monoclonal antibodies for quantitative immunoblots. The percentage of beta-tubulin isotype classes I, II, III, and IVa + IVb mRNA and protein were compared. For beta-tubulin class I that comprises >50% of the beta-tubulin protein in 10 of the 12 cell lines, there was good agreement between mRNA and protein percentages. Agreement between mRNA and protein was also found for beta-tubulin class III. For beta-tubulin classes IVa + IVb, we observed higher protein levels compared to mRNA levels.Beta-tubulin class II protein was found in only four cell lines and in very low abundance. We conclude that quantitative Western blotting is a reliable method for measuring tubulin isotype levels in human cancer cell lines. Inferring protein amounts from mRNA levels should be done with caution, since the correspondence is not one-to-one for all tubulin isotypes.